86 research outputs found
DD-AMG on QPACE 3
We describe our experience porting the Regensburg implementation of the
DD-AMG solver from QPACE 2 to QPACE 3. We first review how the code was
ported from the first generation Intel Xeon Phi processor (Knights Corner) to
its successor (Knights Landing). We then describe the modifications in the
communication library necessitated by the switch from InfiniBand to Omni-Path.
Finally, we present the performance of the code on a single processor as well
as the scaling on many nodes, where in both cases the speedup factor is close
to the theoretical expectations.Comment: 12 pages, 6 figures, Proceedings of Lattice 201
The role of the pregnancy-associated protein glycodelin and its influence on the immune system in non-small-cell lung cancer
Lung cancer remains the major cause of cancer related death worldwide. Recent developments in immunotherapy promise to be a gamechanger in early and advanced disease by overcoming the tumor immune escape. However, current immunotherapeutic approaches cannot be implemented for every patient, some lack a benefit and especially women often suffer from severe side effects or fail to respond to the treatment successfully.
Glycodelin is a glycoprotein which is crucial for the establishment and maintenance of pregnancy. Glycodelin A, one of four glycosylation forms, suppresses the maternal immune system and allows the fertilized egg to invade into the decidual tissue. During pregnancy, it modulates the immune environment at the feto-maternal interface to prevent defense mechanisms towards the fetus as a semi-allograft. Interestingly, high glycodelin protein and corresponding progesterone-associated endometrial protein (PAEP) gene expression were also discovered in lung tumors compared to normal lung tissue.
In the frame of this project I have investigated whether glycodelin in non-small cell lung cancer (NSCLC) shares the immunosuppressive function of glycodelin A known from pregnancy and could therefore serve as a novel target for future immunotherapies.
For my study, I have used the primary cell lines 4950T and 170162T that secrete between 20-100 ng/ml glycodelin into the cell culture supernatant. The glycosylation structure was analyzed by lectin-based enrichment and could show that NSCLC derived glycodelin resembles the glycosylation pattern of glycodelin A isolated from amniotic fluid. The proteins shared high sialylation which is known to be crucial for immunosuppression. It is important to point out that sialic residues were detected weaker in glycodelin derived from 170162T, a NSCLC cell line that originates from a male patient. Thus, the protein might have sex-specific structures and functions. In vitro, NSCLC-derived glycodelin was bound and internalized by immune cells. It did not induce apoptosis but affected gene expression in monocytic and natural killer cells involved in tumor microenvironment and inflammation pathways. By using multiplex immunofluorescence and spatial analysis on 700 tissue samples, I could demonstrate that glycodelin binds to CD8+ T cells and CD163+ (M2) macrophages in tumor and stroma. Thus, glycodelin in NSCLC clearly interacts with surrounding immune cells and might modulate a pro-tumorigenic environment. The analysis of glycodelin in the serum of inoperable immunotherapy-treated NSCLC patients (n = 139) prior to immunotherapy showed that high serum concentrations of glycodelin were associated with a decreased progression-free survival (p < 0.001) of female patients receiving an anti-PD-1 / PD-L1 therapy. Glycodelin levels did not correlate with the hormones progesterone, estradiol, human chorionic gonadotropin (hCG), or testosterone in the serum. Consequently, it could serve as a predictive biomarker and enable better therapy decisions for female patients. As a first approach in vitro, I showed that glycodelin is targetable and that glycodelin binding to immune cells can be inhibited by using a monoclonal anti-glycodelin antibody.
In conclusion, I could demonstrate that glycodelin has high potential of being a novel target in immuno-oncology and predictor of therapy response for NSCLC patients
MRHS multigrid solver for Wilson-clover fermions
We describe our implementation of a multigrid solver for Wilson-clover
fermions, which increases parallelism by solving for multiple right-hand sides
(MRHS) simultaneously. The solver is based on Grid and thus runs on all
computing architectures supported by the Grid framework. We present detailed
benchmarks of the relevant kernels, such as hopping and clover term on the
various multigrid levels, intergrid operators, and reductions. The benchmarks
were performed on the JUWELS Booster system at J\"ulich Supercomputing Centre,
which is based on Nvidia A100 GPUs. For example, solving a
lattice on 16 GPUs, the overall speedup obtained solely from MRHS is about 10x.Comment: 8 pages, 14 figures, proceedings of Lattice 202
Direct determinations of the nucleon and pion terms at nearly physical quark masses
We present a high statistics study of the pion and nucleon light and strange
quark sigma terms using dynamical non-perturbatively improved clover
fermions with a range of pion masses down to MeV and several
volumes, up to , and lattice spacings, fm,
enabling a study of finite volume and discretisation effects for MeV. Systematics are found to be reasonably under control. For the nucleon
we obtain MeV and MeV, or equivalently
in terms of the quark fractions, , and
, where the errors include estimates of both the systematic
and statistical uncertainties. These values, together with perturbative
matching in the heavy quark limit, lead to ,
and . In addition, through the use of the
(inverse) Feynman-Hellmann theorem our results for are shown
to be consistent with the nucleon masses determined in the analysis. For the
pion we implement a method which greatly reduces excited state contamination to
the scalar matrix elements from states travelling across the temporal boundary.
This enables us to demonstrate the Gell-Mann-Oakes-Renner expectation
over our range of pion masses.Comment: 31 pages, 18 figures, v2, small changes to text and figure
pMR: A high-performance communication library
On many parallel machines, the time LQCD applications spent in communication
is a significant contribution to the total wall-clock time, especially in the
strong-scaling limit. We present a novel high-performance communication library
that can be used as a de facto drop-in replacement for MPI in existing
software. Its lightweight nature that avoids some of the unnecessary overhead
introduced by MPI allows us to improve the communication performance of
applications without any algorithmic or complicated implementation changes. As
a first real-world benchmark, we make use of the pMR library in the coarse-grid
solve of the Regensburg implementation of the DD-AMG algorithm. On
realistic lattices, we see an improvement of a factor 2x in pure communication
time and total execution time savings of up to 20%.Comment: 7 pages, 2 figures, Proceedings of Lattice 201
Vaccines under development: group B streptococcus, herpes-zoster, HIV, malaria and dengue
OBJECTIVES: To review the current state of development of streptococcus B, herpes-zoster, HIV, malaria and dengue vaccines. These vaccines were selected both because of imminent commercial release and because of specific problems with their development. SOURCES OF DATA: A review of the literature was performed by means of a MEDLINE search, on the period 1996 to 2006, for the epidemiology and immunology of these diseases, analyzing both the greatest obstacles to creating a vaccine and the current state of research, with emphasis on studies in the most advanced stages. SUMMARY OF THE FINDINGS: Each of the five diseases chosen presents specific problems for vaccine development. Nevertheless, in the majority of cases these have been or are in sight of being resolved, allowing for the prediction that a safe and effective vaccine - or vaccines - will be available in the near future. CONCLUSIONS: Despite the problems faced in developing these vaccines, advances in molecular biology and immunology have made it possible to overcome most obstacles, opening up the prospects for new vaccines.OBJETIVOS: As vacinas contra o estreptococo B, o herpes-zóster, o HIV, a malária e a dengue, selecionadas por critérios de comercialização iminente ou devido a problemas específicos para sua obtenção, foram objeto de uma revisão sobre o estado atual do seu desenvolvimento. FONTE DOS DADOS:Foi realizada revisão da literatura através da MEDLINE no período de 1996 a 2006, sobre a epidemiologia e imunologia das doenças, analisando tanto os maiores problemas para a obtenção de uma vacina como o estado atual dos estudos, com ênfase para os que estavam em fase mais adiantada. SÍNTESE DOS DADOS: Cada uma das cinco doenças escolhidas apresenta problemas específicos para o desenvolvimento de uma vacina. No entanto, a maioria deles já foi ou está em vias de ser resolvido, permitindo prever que uma vacina - ou vacinas - eficaz e segura estará disponível em futuro próximo. CONCLUSÕES:Apesar dos problemas enfrentados para o desenvolvimento dessas vacinas, os avanços da biologia molecular e da imunologia permitiram superar a maioria deles, abrindo a perspectiva para a obtenção de novas vacinas.s115s12
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